Risk of renal stone formation induced by long‐term bed rest could be decreased by premedication with bisphosphonate and increased by resistive exercise

Abstract

Objectives:To clarify the influence of long-term bed rest on renal stone formation and to analyze the mechanism of bed-rest-induced stone formation and prevention by bisphosphonate and bed-rest exercise. Methods: Twenty-five men aged 26-48 years and divided into control (CON: n = 9), exercise (EX: n = 9), and pamidronate (PMD: n = 7) groups, rested on a 6°head-down tilt bed for 90 days. The exercise group carried out resistive exercise every 3 days. Pamidronate (60 mg) was intravenously given 2 weeks before the initiation of bed rest. Abdominal X-ray examination and urine biochemistry were carried out during 90 days of bed rest and 90 days of reloading. Results: Renal stone formation was observed in two (22.2%) and four (44.4%) subjects in the control and exercise groups, respectively. No stone was seen in the pamidronate group. In the exercise group, urinary oxalate and phosphate excretion were significantly higher than in the control group. In the pamidronate group, urinary calcium excretion and relative supersaturation of calcium oxalate and brushite were lower than in the control group throughout the bed-rest and recovery period. Conclusion: Long-term bed-rest-induced renal stone formation was found to be induced by increased urinary calcium and subsequent crystal formation of calcium oxalate and calcium phosphate. Exercise during bed rest for the prevention of bone mineral loss and contracture might increase the risk of renal stone formation. Pamidronate is useful for the prevention of renal stone formation during and after bed rest.

Long-duration bed rest as an analog to microgravity

“…Urinary calcium excretion increases as early as the first day of bed rest, and urinary CTX and NTX excretion significantly increases on the second day of bed rest (6,44). Such increases in urinary calcium along with diminished urine volume (38,58,72) bring concerns about the risk of renal stone formation (47,69,79,122,126). It is not yet clear whether bone resorption activity increases with time of inactivity (72,116) or whether a plateau is reached around the 20th day of bed rest at 50 -150% above pre-bed rest values (48,101).…”

“…Ruml and coworkers (91) report that alendronate prevents hypercalciuria and crystallization of Ca salts induced by a 3 wk of bed rest, and Zerwekh and associates (126) document lower renal stone risk by potassium-magnesium citrate during 5 wk of bed rest. Antiresorptives also appear to prevent the development of renal stones during spaceflight (78). In the USSR 120-day bed rest study with iliac crest biopsies, etidronate treatment decreased bone osteoclastic and osteoblastic activities (120).…”

Space Flight Calcium: Implications for Astronaut Health, Spacecraft Operations, and Earth

“…This increased risk has been documented during both short- and long-duration space missions [103,104,105], as well as in bed rest [106,107,108,109,110]. Given that the occurrence of a kidney stone on orbit would likely result in the medical evacuation of the affected crewmember (and likely end the mission for all crewmembers, given the nature of spacecraft), the likelihood of a kidney stone occurring has warranted a fair amount of attention.…”

Sex‐specific responses of bone metabolism and renal stone risk during bed rest

“…; Okada et al. ). Renal stone risk, typically assessed by calculating relative urine supersaturation, is generally low during bed rest because subjects are encouraged to consume large amounts of fluid, specifically to minimize this risk.…”

“…Bone demineralization during spaceflight and bed rest increases urinary calcium, which alters urine chemistry to favor renal stone formation (Whitson et al 1993(Whitson et al , 1997(Whitson et al , 1999Monga et al 2006;Okada et al 2008). Renal stone risk, typically assessed by calculating relative urine supersaturation, is generally low during bed rest because subjects are encouraged to consume large amounts of fluid, specifically to minimize this risk.…”